Hyperuricemia protects against low bone mineral density, osteoporosis and fractures: a systematic review and meta-analysis

BACKGROUND: Serum uric acid (SUA) accounts for about 50% of extracellular antioxidant activity, suggesting that hyperuricemia may have a protective role in diseases characterized by high levels of oxidative stress, such as osteoporosis. We aimed to meta-analyse data regarding bone mineral density (BMD), osteoporosis and fractures in people with higher SUA vs. lower SUA concentrations. MATERIALS AND METHODS: Two investigators conducted a literature search using PubMed and Scopus, without language restrictions. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used for BMD; risk ratios (RRs) and adjusted odds ratios (ORs) for cross-sectional data. Most possible adjusted hazard ratios (HRs) were used to assess the association between baseline SUA and incident fractures. RESULTS: Of 1405 initial hits, 19 studies were eligible including a total of 55 859 participants. Subjects with higher SUA levels had significantly higher BMD values for the spine (six studies; SMD = 0·29; 95% CI: 0·22-0·35; I2 = 47%), total hip (seven studies; SMD = 0·29; 95% CI: 0·24-0·34; I2 = 33%) and femoral neck (six studies; SMD = 0·25; 95% CI: 0·16-0·34; I2 = 71%). Simple correlation analyses substantially confirmed these findings. An increase of one standard deviation in SUA levels reduced the number of new fractures at follow-up (three studies; HR = 0·83; 95% CI: 0·74-0·92; I2 = 0%). No significant differences between men and women emerged, although data about women were limited. CONCLUSIONS: Hyperuricemia was found independently associated with BMD and fractures, supporting a protective role for uric acid in bone metabolism disorders.